Cell therapy products are required to be safe and effective with minimum side effects to the patient but also must be free from contamination with adventitious microorganisms, which may cause infection or adverse reactions in patients or affect the therapeutic activity by degrading the product. An adventitious agent is defined by the World Health Organization (WHO) as “contaminating microorganism of the cell culture or starting/raw materials, including bacteria, fungi, mollicutes (mycoplasmas or spiroplasmas), mycobacteria, rickettsia, protozoa, parasites, agents causing transmissible spongiform encephalopathy (TSE) and viruses that have been unintentionally introduced into the manufacturing process of a biological product”. The 21 CFR §1271 regulations enforce that manufacturers of human cells, tissues, and cellular and tissue-based products follow current good tissue practices. The 2020 US FDA Guidance for Industry, Human Gene Therapy Investigational New Drug Applications, recommends that measures be taken to ensure aseptic processing and preventing microbial contamination.
Cell-Based Advanced Therapies and Tissue-Based Products 〈1046〉 provides a comprehensive overview of considerations for the development of cell-based advanced therapies and tissue-based products and describes a general guidance for the manufacturing of cell therapy products. This chapter provides a greater focus on associated microbial contamination risks and challenges, detection of microbial contamination, and practical guidance specific to microbial control strategies for cell therapy products.
Cell therapy products are susceptible to diverse cell collection and manufacturing processes, which may cover steps such as donor selection, cell collection, infectious agent testing, cell transformation and expansion, packaging, storage and administration, and cell therapy microbial contamination testing and release. Cell therapies, especially autologous products, are manufactured in small volumes, often in a single lot, have unique manufacturing processes related to a single product, and may have many aseptic manipulations. This distinguishes them from large-scale classical pharmaceutical products for which the general current good manufacturing practice (CGMP) guidelines were initially intended. Allogenic products may be derived from master and working cell banks that are subject to cell transformation and expansion, cryoprotection, and frozen storage to treat multiple patients.
For most cell therapy products, there is no terminal sterilization step in the process, so they cannot be claimed as “sterile products”. However, they are manufactured under conditions that would prevent microbial contamination to be categorized as “aseptically manufactured products”.
As cell therapy products need to be manufactured aseptically, tight control of microbial contamination needs to be put in place during the product lifecycle. A microbial control strategy that would fit every type of cell therapy product is challenging, but a common strategy is possible. Sterility Assurance 〈1211〉 provides the general concepts and principles involved in the preparation of materials that must be sterile. Further considerations focusing more on the aseptic manufacturing of cell therapy products are outlined in this chapter. In addition, a risk-based approach to better mitigate the potential weaknesses of each process, focus resources on the most critical contamination points, and ensure the timely release of product to the patient will be outlined.
Source from USP and Please refer to USP for details:
RTU(ready to use) 2ml COP vial
Polymer Vial for cell and gene therapies
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